This project will utilize cultured islet cells from normal and diabetes mice in attempts to establish any abnormalities in islet cell metabolism that may persist under chemically defined conditions in vitro. Any parameters observed to be abnormal in vitro will be evaluated in the intact diabetic animals to determine if a primary genetic defect is being expressed. We have already observed increased glucagon secretion in cultures of islet cells from diabetes mice of the severely afflicted diabetes strains as early as 4 days of postnatal development and prior to an elevation in insulin release in diabetic cell cultures. The relationship between this abnormality and the subsequent development of juvenile diabetes is being investigated. Morphological studies have shown a relative increase in the area occupied by somatostatin-containing delta cells in islets of diabetes mice but only on the background that leads to severe diabetes. Since in these diabetic islets there are greatly increased cell surface contacts between delta cells and beta cells, a role for delta cells in the control of excessive insulin secretion by direct cell-to-cell communication is under investigation.